CN110123745A - A kind of Taxol injection liquid and preparation method thereof being resistant to terminal sterilization - Google Patents
A kind of Taxol injection liquid and preparation method thereof being resistant to terminal sterilization Download PDFInfo
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- CN110123745A CN110123745A CN201910566115.XA CN201910566115A CN110123745A CN 110123745 A CN110123745 A CN 110123745A CN 201910566115 A CN201910566115 A CN 201910566115A CN 110123745 A CN110123745 A CN 110123745A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The present invention relates to a kind of Taxol injection liquid and preparation method thereofs for being resistant to terminal sterilization, belong to technical field of medicine.The preparation method of paclitaxel injection of the invention, comprising the following steps: (1) taxol of recipe quantity is added into the polyoxyethylene of recipe quantity (35) castor oil, and high-speed stirred is sheared；(2) dehydrated alcohol of recipe quantity is added into solution, stirring is uniformly mixed to solution and carries out deoxygenation；(3) aseptic filtration, filling deoxygenation, sealing, high-temperature sterilization are carried out to step (2) acquired solution.Taxol injection liquid and preparation method thereof of the invention, by changing charging sequence, wrap up polyoxyethylene (35) castor oil to taxol, it is possible to reduce mass degradation and decomposition of the taxol in terminal sterilization technique, finally obtained paclitaxel injection quality is good, stability is high.
Description
Technical field
The present invention relates to a kind of Taxol injection liquid and preparation method thereof, in particular to a kind of taxol note for being resistant to terminal sterilization
Liquid and preparation method thereof is penetrated, technical field of medicine is belonged to.
Background technique
Taxol is that a kind of isolated antineoplastic is extracted from taxaceae Chinese yew genus plants Chinese yew.It has
There is unique mechanism of action, by inducing and promoting tubulin polymerization, assembly and stablize micro-pipe effect, prevents tumour cell
Growth, it is significant in efficacy to oophoroma, breast cancer, head-neck carcinoma, lung cancer in non-cellule type and prostate cancer, it is broad-spectrum anti-cancer drug.
Taxol and its injection are developed by Bristol-Myers Squibb company earliest, obtain within 1992 FDA approval for the first time into
Enter American market, is worldwide widely used at present.
Due to paclitaxel structure complexity, unstable to heat, alkali, illumination, facile hydrolysis, chiral centre are easily inverted, using end
High-temperature sterilizing process is held, taxol active material is be easy to cause to degrade, content of taxol drops in finally obtained injection
Low, related substance increases, and quality reduces.Thus, industry mainstream degerming technique is mainly by the way of aseptic filtration to purple at present
China fir alcohol injection carries out degerming, does not carry out terminal sterilization processing, but the sterility assurance level of aseptic filtration to Taxol injection
Significantly lower than terminal sterilization.
Summary of the invention
It is an object of the invention to overcome taxol thermal stability bad, can not terminal sterilization the shortcomings that, provide a kind of resistance to
By the preparation method of the paclitaxel injection of terminal sterilization, the sterility assurance level of paclitaxel injection is improved.
In order to achieve the above-mentioned object of the invention, the present invention provides following technical schemes:
A kind of preparation method for the paclitaxel injection being resistant to terminal sterilization, comprising the following steps:
(1) taxol of recipe quantity is added into the polyoxyethylene of recipe quantity (35) castor oil, and in revolving speed >=4000rpm item
High-speed stirred shears 120min or more under part, obtains solution A；
(2) dehydrated alcohol of recipe quantity is added into solution A, stirring to solution is uniformly mixed, and obtains solution B；
(3) deoxygenation is carried out to solution B；
(4) aseptic filtration, filling deoxygenation, sealing, high-temperature sterilization are carried out to through step (3) treated solution B.
The preparation method of above-mentioned paclitaxel injection, in step (1), by being cut at a high speed under conditions of 4000rpm or more
The mixing liquid 120min or more for cutting taxol and polyoxyethylene (35) castor oil, pre-processes taxol, can will be purple
China fir alcohol is dissolved in polyoxyethylene (35) castor oil, and realizes polyoxyethylene (35) castor oil to the package of taxol.Then right
Pretreated taxol and polyoxyethylene (35) castor oil are handled to obtain into according to the technique of step (2), (3) and (4)
Product paclitaxel injection.Wherein, step (2), (3) and (4) can be the existing any work for being able to achieve paclitaxel injection preparation
Skill, details are not described herein.Wherein, high-temperature sterilization refers to that sterilising temp exists121 DEG C or more high-temperature sterilizing process.Of the invention
Taxol injection liquid and preparation method thereof, by polyoxyethylene (35) castor oil to taxol before dehydrated alcohol dissolution taxol is added
It is wrapped up, it is possible to reduce mass degradation of the taxol in terminal sterilization technique (the high-temperature sterilization step i.e. in step (4))
And decomposition, finally obtained paclitaxel injection quality is good, stability is high.Further, solution B is removed in step (3)
Oxygen reduces the oxygen content in paclitaxel injection, it is possible to reduce oxidation of the oxygen to taxol in storing process further extends
The holding time of paclitaxel injection.
Preferably, in step (1), the revolving speed of the high speed shear is 4000rpm, shear time 120min.
Preferably, in step (3), deoxygenation is carried out by being passed through nitrogen into solution B.
Preferably, in step (3), to dissolved oxygen content≤0.5mg/L of the solution B deoxygenation into solution.It is molten in solution B
When solving oxygen content≤0.5mg/L, the stability of paclitaxel injection is more preferable, and the holding time significantly extends.It is furthermore preferred that solution
Dissolved oxygen content≤0.2mg/L of the B deoxygenation into solution.
Preferably, in step (4), the aseptic filtration step is that solution B is passed through 2 0.22 μm of PVDF filter element filterings.
Lower using the visible foreign matters risk in twice filter element filtering paclitaxel injection, paclitaxel injection does not tend to have crystallization and is precipitated
Object, injection quality are more preferable.
Preferably, in step (4), in the filling oxygen scavenging step, deoxygenation is carried out by being passed through nitrogen into filling liquid.
The deoxygenation of filling bottle head space can be further reduced during injection saves and be oxidized by oxygen, being passed through nitrogen deoxygenation can also be to Japanese yew
Alcohol injection carries out protective barrier, can further extend the holding time of paclitaxel injection.
Preferably, in step (4), in the filling oxygen scavenging step, deoxygenation to filling bottle head space oxygen content≤10%(v/v),
That is the aerial volume accounting of oxygen is less than 10%.As filling bottle head space oxygen content≤10%(v/v) when, the oxygen in gas will not
It is dissolved in taxol liquid, can guarantee that there is lower oxygen content in paclitaxel injection, it is not easy to oxidation reaction occurs,
The holding time of paclitaxel injection is longer.It is furthermore preferred that in step (4), in the filling oxygen scavenging step, deoxygenation to filling bottle
Head space oxygen content≤5%(v/v), i.e. the aerial volume accounting of oxygen is less than 5%.
Preferably, in step (4), the high-temperature sterilization step is, using water-bath sterilization cabinet, in 121 DEG C ~ 125 DEG C conditions
Under, sterilize 8 ~ 15min.The mode of water-bath sterilization, sterilising temp are easier to control, and are gone out within the temperature range of 121 DEG C ~ 125 DEG C
8 ~ 15min of bacterium, high temperature degradation is less likely to occur thermally sensitive taxol, and sterilization effect is good.It is furthermore preferred that using water-bath
Sterilizing cabinet sterilizes 12 minutes at 121 DEG C.
Preferably, moisture content≤0.6wt.% of finished product obtained by rate-determining steps (4).By to by the moisture control in finished product
System is in 0.6wt.% and hereinafter, can significantly extend the holding time of paclitaxel injection.It is furthermore preferred that obtained by rate-determining steps (4)
Moisture content≤0.4wt.% of finished product.
Preferably, moisture content of finished products obtained by step (4) is controlled in the following manner, before step (1), use is anhydrous
Ethanol washing liquid dispensing container and pipeline 3 times or more.The moisture content in paclitaxel injection is controlled by preparation process
System, has simplified the dewatering process of paclitaxel injection, other quality risks that can be introduced to avoid dewatering process.
Compared with prior art, beneficial effects of the present invention:
1, polyoxyethylene may be implemented by the pretreating process to taxol in Taxol injection liquid and preparation method thereof of the invention
(35) castor oil, can be final to obtain to avoid mass degradation of the taxol in terminal high-temperature sterilizing process to the package of taxol
The paclitaxel injection quality arrived is good, stability is high.
2, Taxol injection liquid and preparation method thereof of the invention, by with liquid deoxygenation to 0.5mg/L or less；Filling deoxygenation is extremely pushed up
Sky 10% is hereinafter, can significantly extend the holding time of paclitaxel injection.
3, Taxol injection liquid and preparation method thereof of the invention, can be with by the control to moisture content in paclitaxel injection
The hydrolysis during paclitaxel injection saves is reduced, when the moisture content in paclitaxel injection is lower than 0.6wt.%, Japanese yew
The holding time of alcohol injection significantly extends, and the quality of paclitaxel injection significantly improves.
Detailed description of the invention:
Fig. 1 is embodiment 1 in relation to substance test map.
Fig. 2 is comparative example 1 in relation to substance test map.
Specific embodiment
Below with reference to test example and specific embodiment, the present invention is described in further detail.But this should not be understood
It is all that this is belonged to based on the technology that the content of present invention is realized for the scope of the above subject matter of the present invention is limited to the following embodiments
The range of invention.
Test example:
Prescription information
Embodiment 1
The Taxol injection liquid and preparation method thereof of the tolerance terminal sterilization of embodiment 1, comprising the following steps:
(1) taxol of recipe quantity is added into the polyoxyethylene of recipe quantity (35) castor oil, and in revolving speed >=4000rpm item
High-speed stirred shears 120min or more under part, obtains solution A；It is specific as follows:
Agitation Tank and pipeline are with dehydrated alcohol drip wash 3 times；Polyoxyethylene (35) castor oil of recipe quantity is taken to be added in Agitation Tank；So
The taxol of recipe quantity is added in Agitation Tank afterwards, high-speed stirred shears 120min under the conditions of 4000rpm, simultaneously by taxol dissolution
Package obtains solution A into polyoxyethylene (35) castor oil.
(2) dehydrated alcohol of recipe quantity is added into solution A, stirring to solution is uniformly mixed, and obtains solution B；
(3) deoxygenation is carried out to solution B；It is specific as follows:
Clean nitrogen is passed through into solution B, until dissolved oxygen content≤0.2mg/L in solution B.
(4) aseptic filtration, filling deoxygenation, sealing, high-temperature sterilization are carried out to through step (3) treated solution B.Specifically such as
Under:
Be passed through the pressurization of clean nitrogen to Agitation Tank, by solution B after 2 0.22 μm of PVDF filter element filterings filling to middle borosilicate glass
In glass injection bottle, filling front and back nitrogen charging deoxygenation controls bottle headspace oxygen oxygen content≤5%(v/v)；Then it jumps a queue, roll lid.It will fill
Product are dressed up in water-bath sterilization cabinet, are sterilized 12 minutes under the conditions of 121-125 DEG C.
Embodiment 2
The preparation method of the paclitaxel injection of the tolerance terminal sterilization of embodiment 2, comprising the following steps:
(1) taxol of recipe quantity is added into the polyoxyethylene of recipe quantity (35) castor oil, and in revolving speed >=4000rpm item
High-speed stirred shears 120min or more under part, obtains solution A；It is specific as follows:
Agitation Tank and pipeline are with dehydrated alcohol drip wash 3 times；Polyoxyethylene (35) castor oil of recipe quantity is taken to be added in Agitation Tank；So
The taxol of recipe quantity is added in Agitation Tank afterwards, high-speed stirred shears 120min under the conditions of 4000rpm, simultaneously by taxol dissolution
Package obtains solution A into polyoxyethylene (35) castor oil.
(2) dehydrated alcohol of recipe quantity is added into solution A, stirring to solution is uniformly mixed, and obtains solution B；
(3) deoxygenation is carried out to solution B；It is specific as follows:
Clean nitrogen is passed through into solution B, until dissolved oxygen content≤0.5mg/L in solution B.
(4) aseptic filtration, filling deoxygenation, sealing, high-temperature sterilization are carried out to through step (3) treated solution B.Specifically such as
Under:
Be passed through the pressurization of clean nitrogen to Agitation Tank, by solution B after 2 0.22 μm of PVDF filter element filterings filling to middle borosilicate glass
In glass injection bottle, filling front and back nitrogen charging deoxygenation controls bottle headspace oxygen oxygen content≤10%(v/v)；Then it jumps a queue, roll lid.It will fill
Product are dressed up in water-bath sterilization cabinet, are sterilized 12 minutes under the conditions of 121-125 DEG C.
Comparative example:
Prescription information
Comparative example 1
The preparation method of the paclitaxel injection of comparative example 1, comprising the following steps:
(1) taxol of recipe quantity is added into the dehydrated alcohol of recipe quantity, stirring is uniformly mixed solution, obtains solution A；Specifically
It is as follows:
Agitation Tank and pipeline are with dehydrated alcohol drip wash 3 times；The dehydrated alcohol of recipe quantity is taken to be added in Agitation Tank；Then by recipe quantity
Taxol be added Agitation Tank in, stirring make solution be uniformly mixed.
(2) polyoxyethylene (35) castor oil of recipe quantity is added into solution A, continues stirring to solution and is uniformly mixed, obtain
Solution B；
Polyoxyethylene (35) castor oil of recipe quantity is taken to be added in Agitation Tank；High-speed stirred shears 120min under the conditions of 4000rpm,
It is uniformly mixed to solution, obtains solution B；
(3) deoxygenation is carried out to solution B；It is specific as follows:
Clean nitrogen is passed through into solution B, until dissolved oxygen content≤0.2mg/L in solution B.
(4) aseptic filtration, filling deoxygenation, sealing, high-temperature sterilization are carried out to through step (3) treated solution B.Specifically such as
Under:
Be passed through the pressurization of clean nitrogen to Agitation Tank, by solution B after 2 0.22 μm of PVDF filter element filterings filling to middle borosilicate glass
In glass injection bottle, filling front and back nitrogen charging deoxygenation controls bottle headspace oxygen oxygen content≤5%(v/v)；Then it jumps a queue, roll lid.It will fill
Product are dressed up in water-bath sterilization cabinet, are sterilized 12 minutes under the conditions of 121-125 DEG C.
Comparative example 2
The preparation method of the paclitaxel injection of comparative example 2, comprising the following steps:
(1) taxol of recipe quantity is added into the polyoxyethylene of recipe quantity (35) castor oil, and in revolving speed >=4000rpm item
High-speed stirred shears 120min or more under part, obtains solution A；It is specific as follows:
Agitation Tank and pipeline are with dehydrated alcohol drip wash 3 times；Polyoxyethylene (35) castor oil of recipe quantity is taken to be added in Agitation Tank；So
The taxol of recipe quantity is added in Agitation Tank afterwards, high-speed stirred shears 120min under the conditions of 4000rpm, simultaneously by taxol dissolution
Package is into polyoxyethylene (35) castor oil.
(2) dehydrated alcohol of recipe quantity is added into solution A, stirring to solution is uniformly mixed, and obtains solution B；
(3) deoxygenation is carried out to solution B；It is specific as follows:
Clean nitrogen is passed through into solution B, until the dissolved oxygen content about 5mg/L or so in solution B.
(4) aseptic filtration, filling deoxygenation, sealing, high-temperature sterilization are carried out to through step (3) treated solution B.Specifically such as
Under:
Be passed through the pressurization of clean nitrogen to Agitation Tank, by solution B after 2 0.22 μm of PVDF filter element filterings filling to middle borosilicate glass
In glass injection bottle, filling front and back nitrogen charging deoxygenation controls bottle headspace oxygen oxygen content≤5%(v/v)；Then it jumps a queue, roll lid.It will fill
Product are dressed up in water-bath sterilization cabinet, are sterilized 12 minutes under the conditions of 121-125 DEG C.
Comparative example 3
The preparation method of the paclitaxel injection of comparative example 3, comprising the following steps:
(1) taxol of recipe quantity is added into the polyoxyethylene of recipe quantity (35) castor oil, and in revolving speed >=4000rpm item
High-speed stirred shears 120min or more under part, obtains solution A；It is specific as follows:
Agitation Tank and pipeline are with dehydrated alcohol drip wash 3 times；Polyoxyethylene (35) castor oil of recipe quantity is taken to be added in Agitation Tank；So
The taxol of recipe quantity is added in Agitation Tank afterwards, high-speed stirred shears 120min under the conditions of 4000rpm, simultaneously by taxol dissolution
Package is into polyoxyethylene (35) castor oil.
(2) dehydrated alcohol of recipe quantity is added into solution A, stirring to solution is uniformly mixed, and obtains solution B；
(3) deoxygenation is carried out to solution B；It is specific as follows:
Clean nitrogen is passed through into solution B, until dissolved oxygen content≤0.2mg/L in solution B.
(4) aseptic filtration, filling, sealing, high-temperature sterilization are carried out to through step (3) treated solution B.It is specific as follows:
Be passed through the pressurization of clean nitrogen to Agitation Tank, by solution B after 2 0.22 μm of PVDF filter element filterings filling to middle borosilicate glass
In glass injection bottle；Then it jumps a queue, roll lid.By filling finished product in water-bath sterilization cabinet, sterilize 12 points under the conditions of 121-125 DEG C
Clock.(filling front and back does not carry out nitrogen charging deoxygenation, 20%) bottle head space oxygen content is about
Comparative example 4
The preparation method of the paclitaxel injection of comparative example 4, comprising the following steps:
(1) taxol of recipe quantity is added into the polyoxyethylene of recipe quantity (35) castor oil, and in revolving speed >=4000rpm item
High-speed stirred shears 120min or more under part, obtains solution A；It is specific as follows:
Agitation Tank and pipeline are clean with water for injection drip wash；Polyoxyethylene (35) castor oil of recipe quantity is taken to be added in Agitation Tank；
Then the taxol of recipe quantity is added in Agitation Tank, high-speed stirred shears 120min under the conditions of 4000rpm, and taxol is dissolved
And it wraps up into polyoxyethylene (35) castor oil.
(2) dehydrated alcohol of recipe quantity is added into solution A, stirring to solution is uniformly mixed, and obtains solution B；
(3) deoxygenation is carried out to solution B；It is specific as follows:
Clean nitrogen is passed through into solution B, until dissolved oxygen content≤0.2mg/L in solution B.
(4) aseptic filtration, filling deoxygenation, sealing, high-temperature sterilization are carried out to through step (3) treated solution B.Specifically such as
Under:
Be passed through the pressurization of clean nitrogen to Agitation Tank, by solution B after 2 0.22 μm of PVDF filter element filterings filling to middle borosilicate glass
In glass injection bottle, filling front and back nitrogen charging deoxygenation controls bottle headspace oxygen oxygen content≤5%(v/v)；Then it jumps a queue, roll lid.It will fill
Product are dressed up in water-bath sterilization cabinet, are sterilized 12 minutes under the conditions of 121-125 DEG C.
Laboratory test results and analysis:
The sample for taking each embodiment and comparative example to prepare is detected, and following experimental data is obtained:
In table 1: in the experimental data of embodiment 1, experimental test data before high-temperature sterilization, test sample is according to implementation
The sample that the paclitaxel injection of the method preparation of example 1 takes out before high-temperature sterilization.Remainder data be according to each embodiment and
Final paclitaxel injection made from the preparation method (after terminal high-temperature sterilization) of comparative example.
In table 2: the experimental test data of each embodiment and comparative example be to corresponding test sample in table 1 in high temperature
Detection data after being placed 30 days under the conditions of (60 DEG C).
Each embodiment and comparative example of table 1 prepares gained 0 day detection project of paclitaxel injection
From the experimental data of table 1:
In the testing result of embodiment 1 and embodiment 2, the content in relation to substance is examined significantly lower than the experimental data of each comparative example
Survey result.
Taxol injection prepared by embodiment 1, before high-temperature sterilization and after high-temperature sterilization, every Testing index is without larger
The change of divergence.And the paclitaxel injection prepared according to comparative example 1, after high-temperature sterilization, related content of material in injection
It is significantly raised compared to the experimental test data of embodiment 1.
It can be seen that: the present invention changes solution system environment, the control of taxol by the pretreating process to taxol
Moisture content in the oxygen residual quantity and configuration process and finished product of preparation process uses the technique of terminal sterilization in taxol,
The quality of paclitaxel injection is significantly improved, the sterility assurance level of taxol is improved.
Each embodiment and comparative example of table 2 prepares gained paclitaxel injection high temperature (60 DEG C) 30 days detection projects
According to the experimental data of Tables 1 and 2:
Paclitaxel injection prepared by embodiment 1 and embodiment 2 is placed 30 days under the conditions of 60 DEG C of high temperature, and indices are without obvious
Variation, and its related content of material is significantly lower than the related content of material of each comparative example.
In each comparative example, rising by a relatively large margin is presented in relation to content of material.The Taxol injection of each embodiment preparation
The liquid pot-life is obviously than the paclitaxel injection storage life limit for length of each comparative example preparation.
It can be seen that (1) it is of the invention taxol preparation method preparation the paclitaxel injection holding time it is longer.
Claims (10)
1. a kind of Taxol injection liquid and preparation method thereof for being resistant to terminal sterilization, it is characterised in that the following steps are included:
(1) taxol of recipe quantity is added into the polyoxyethylene of recipe quantity (35) castor oil, and in revolving speed >=4000rpm item
High-speed stirred shears 120min or more under part, obtains solution A；
(2) dehydrated alcohol of recipe quantity is added into solution A, stirring to solution is uniformly mixed, and obtains solution B；
(3) deoxygenation is carried out to solution B；
(4) aseptic filtration, filling deoxygenation, sealing, high-temperature sterilization are carried out to through step (3) treated solution B.
2. Taxol injection liquid and preparation method thereof according to claim 1, it is characterised in that: in step (3), by solution
It is passed through nitrogen in B and carries out deoxygenation.
3. Taxol injection liquid and preparation method thereof according to claim 1 or 2, it is characterised in that: in step (3), to solution B
Dissolved oxygen content≤0.5mg/L of the deoxygenation into solution.
4. Taxol injection liquid and preparation method thereof according to claim 1 or 2, it is characterised in that: in step (3), to solution B
Dissolved oxygen content≤0.2mg/L of the deoxygenation into solution.
5. Taxol injection liquid and preparation method thereof according to claim 1, it is characterised in that: in step (4), the degerming
Filter step is that solution B is passed through 2 0.22 μm of PVDF filter element filterings.
6. Taxol injection liquid and preparation method thereof according to claim 1, it is characterised in that: described filling to remove in step (4)
In oxygen step, deoxygenation to filling bottle head space oxygen content≤10%(v/v).
7. Taxol injection liquid and preparation method thereof according to claim 1, it is characterised in that: described filling to remove in step (4)
In oxygen step, deoxygenation to filling bottle head space oxygen content≤5%(v/v).
8. Taxol injection liquid and preparation method thereof according to claim 1, it is characterised in that: finished product obtained by rate-determining steps (4)
Moisture content≤0.6wt.%.
9. Taxol injection liquid and preparation method thereof according to claim 1, it is characterised in that: finished product obtained by rate-determining steps (4)
Moisture content≤0.4wt.%.
10. Taxol injection liquid and preparation method thereof according to claim 8 or claim 9, it is characterised in that: in the following manner to step
Suddenly moisture content of finished products obtained by (4) is controlled, before step (1), with dehydrated alcohol wash liquid dispensing container and pipeline 3 times and with
On.
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| CN114344251A (en) * | 2020-09-29 | 2022-04-15 | 北京新领先医药科技发展有限公司 | Preparation method of paclitaxel injection |
| CN113712912A (en) * | 2021-09-17 | 2021-11-30 | 杭州上禾健康科技有限公司 | Terbutaline sulfate oral liquid and production method thereof |
| CN116983259A (en) * | 2023-09-27 | 2023-11-03 | 成都瑞尔医药科技有限公司 | Preparation method of etoposide injection |
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